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New results from the ACROSS 2 Phase III trial demonstrate that aumolertinib combined with platinum-pemetrexed chemotherapy significantly improves progression-free survival compared to aumolertinib monotherapy in patients with advanced/metastatic non-small cell lung cancer (NSCLC) harboring EGFR sensitizing mutations and concomitant tumor suppressor gene mutations.

The results were presented by Dr. Jie Wang, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital in China, at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC).

Aumolertinib is an oral, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used to treat EGFR-mutated NSCLC.

Patients with EGFR concomitant mutations typically face a poor prognosis and, until now, have had no standard treatment regimen in clinical practice. Previous studies have suggested that an EGFR-TKI combined with chemotherapy may provide better efficacy than an EGFR-TKI alone.

ACROSS 2 is the first global, multicenter, open-label, randomized, controlled Phase III trial to address this question, according to Dr. Wang.

In ACROSS 2 (NCT04500717), patients with histologically confirmed stage IIIB–IV NSCLC harboring EGFR sensitizing mutations and tumor suppressor gene mutations, and with ECOG performance status 0–1, were randomized 1:1 to receive either aumolertinib 110 mg daily plus carboplatin (AUC=5) and pemetrexed 500 mg/m2 every three weeks, or aumolertinib monotherapy until disease progression. Stratification factors included EGFR mutation type (Ex19del/L858R) and presence of CNS metastases.

The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS), and safety.

Dr. Wang reported that:

Dr. Wang reported that the addition of chemotherapy did not alter aumolertinib's safety profile and no new safety signals were observed.

"This Phase III trial provides the first evidence that aumolertinib combined with platinum-pemetrexed offers a statistically significant PFS benefit over monotherapy for this patient population, with a manageable safety profile, " he said.